Department of Infection and Immunity, University of Sheffield, Sheffield, United Kingdom.
Curr Opin Pharmacol. 2011 Aug;11(4):397-403. doi: 10.1016/j.coph.2011.06.007. Epub 2011 Jul 6.
Neutrophils are key innate immune effector cells that are rapidly recruited to sites of infection and inflammation to provide early defence against invading microorganisms. This function is facilitated by the expression of Toll-like receptor (TLR) family members by neutrophils, allowing the recognition of an extensive repertoire of pathogen-associated molecular patterns (PAMPs) and thus triggering the response to invading pathogens. TLR activation leads to important cellular processes including reactive oxygen species (ROS) generation, cytokine production and increased survival, all of which can contribute to the pathogenesis of chronic inflammation when signalling becomes dysregulated. In turn, inflammation and tissue injury results in the release of endogenous TLR ligands, known as damage-associated molecular patterns (DAMPs), which are a rapidly growing class of potent inflammatory stimuli. DAMPs act in an autocrine manner, alerting the host of damage, but can also amplify inflammation leading to further tissue damage. This review highlights recent literature on neutrophil TLR function and regulation during disease, and provides an overview of the recently emerging area of neutrophil responses to DAMPs.
中性粒细胞是先天免疫效应细胞的关键，可迅速募集到感染和炎症部位，为抵御入侵的微生物提供早期防御。这种功能是通过中性粒细胞表达 Toll 样受体 (TLR) 家族成员来实现的，使它们能够识别广泛的病原体相关分子模式 (PAMPs)，从而触发对入侵病原体的反应。TLR 激活导致重要的细胞过程，包括活性氧 (ROS) 的产生、细胞因子的产生和存活能力的提高，所有这些都可能导致慢性炎症的发病机制失调。反过来，炎症和组织损伤导致内源性 TLR 配体的释放，这些配体被称为损伤相关分子模式 (DAMPs)，它们是一类迅速增长的强效炎症刺激物。DAMPs 通过自分泌方式发挥作用，提醒宿主组织损伤，但也可以放大炎症反应，导致进一步的组织损伤。本综述强调了有关疾病期间中性粒细胞 TLR 功能和调节的最新文献，并概述了中性粒细胞对 DAMPs 反应的新兴领域。
